Contact PD/PI: Park, Kevin (Kyung) Reconnection of Optic Nerve Poor regeneration of retinal ganglion cell (RGC) axons is a major obstacle for treating ocular trauma and optic neuropathies. There are as yet no therapies to repair optic nerve once the damage is done. Our past studies have demonstrated that simultaneous modulation of genes and neurotrophic factors promotes long distance regeneration of some RGCs in adult mice. However, promoting axons not only to regenerate into the lesion, but to travel long distances and reconnect their central targets is still a major challenge. In fact, we and others have reported various degrees of axon misguidance where few axons reinnervate brain targets while many others fail to do so. It is unclear what cellular and molecular factors contribute to the limited (or successful) pathfinding and target re-innervation. At present, very little is known about axon guidance mechanisms in adult mammalian visual system after injury. The overall goal of this proposal is to; i) establish an effective approach that promotes regeneration, reconnection of RGC axons and recovery of functions, ii) harness a new imaging technique (3Dtrace) to examine cell type-specific regeneration and reconnection, and iii) assess whether inactivating axon repulsive signaling improves target re-innervation. Identifying strategies to further increase regeneration and re-innervation in the brain represents critical future studies. Results obtained from these studies will provide invaluable information on developing future therapies to repair degenerated optic nerve after trauma or in diseases.